This research will expand upon Seek-Test-Treat-Retain (STTR) strategies based on HIV testing and treatment of individuals with established HIV infection. The overall objective is to improve the efficacy of STTR strategies by specifically intervening to reduce the impact of HIV transmission risk behaviors among individuals with acute (AHI), recent (RHI) and established HIV infection, especially those with substance use disorders (including alcohol). This research will be conducted in Lima, Peru where substance misuse contributes greatly to HIV transmission among MSM. Novel within this proposal is the investigation of the impact on community- wide HIV transmission of intervening with individuals at various stages of HIV infection (and therefore infectivity) with antiretroviral (ART) and evidence-based treatments for alcohol use disorders (AUDs). We intend to provide best-practices for community mobilization and partner services to increase the number of at-risk MSM tested (seek);expansion of testing algorithms to detect AHI, RHI and established infection (test);linkage to care and timely ART (treat);and promotion of continued HIV care and treatment (retain). Widespread HIV testing will use 4th generation EIA assays and pooled NAAT testing to detect AHI. Specific Aim 1 will investigate the population-level impact of drug and alcohol use on HIV transmission by examining the role of MSM who report substance use (mostly alcohol and cocaine) in transmission clusters identified through partner tracing and phylogenetic analysis. This analysis will also include modeling of the contribution of men with AHI or RHI vs. established HIV infection to transmission among networked populations, such as MSM. HIV viral load (VL) in semen will be measured over a 6 month period in MSM with AHI and RHI who will be randomized to immediate or delayed ART. These data as well as plasma VL will be used to estimate the effect of ART on infectivity and the potential impact of non-adherence during this period. Modeling of the population effect of a combination intervention to reduce onward transmission associated with substance abuse in men with AHI or established infection will include the following data: drug and alcohol use;frequency of detection of AHI and successful linkage to care and treatment;sexual network analysis including impact of substance use;effect of ART on genital tract VL;retention of individuals, including those with AHI, in care;medication adherence;as well as other intervention process data. Specific Aim 2 will focus on alcohol, the "drug of choice" among MSM in Lima. Using a placebo-controlled trial, we will test the efficacy of extended release naltrexone (NTX-XR) in improving HIV and alcohol treatment outcomes, including HIV risk behaviors, associated with alcohol use among MSM with AUDs at all stages (acute, recent and established) of HIV infection. Aim 2 data will also be used to model the potential additional benefit on a population level of including substance-use interventions to reduce unsafe sex and improve ART adherence in STTR interventions. PUBLIC HEALTH RELEVANCE: This study will assess the feasibility and potential impact of incorporating interventions to reduce high rates of onward transmission associated with acute HIV infection (AHI) and unsafe sex practices and poor medication adherence due to alcohol use. These results will inform community-based seek-test-treat-retain (STTR) interventions and HIV/AIDS program development.